Age-dependent Mitochondrial Abnormalities and Structural Changes in Rat Kidney Are Delayed by Adult-onset Calorie Restriction
S.H. McKiernan, V.C. Tuen, J.M. Aiken
University of Wisconsin, Department of Animal Health and Biomedical Sciences, 1656 Linden Drive, Madison, WI 53706, USA
Mitochondrial and structural changes were examined in aging male
Fischer 344 x Brown Norway rat kidneys and the effect of adult-onset
calorie restriction on those changes determined. Kidney morphology and
electron transport system (ETS) enzyme activities were analyzed in
frozen histological kidney sections from 18-, 24-, 30-, and 36-month
old ad libitum (AL) fed rats and 24-, 30-, and 36- month 40% calorie
restricted (CR) rats. Significant age-related increases in
glomerulosclerosis, tubular atrophy, interstitial fibrosis, and
vascular wall thickening for the AL rats were observed. CR rats also
had age-related increases in glomerulosclerosis, interstial fibrosis
and vascular wall thickening, but not in tubular atrophy; however,
adult-onset CR significantly attenuated all four indices at 36-months.
Dual staining for cytochrome c oxidase (COX) and succinate
dehydrogenase identified COX deficient cells. The number of tubules
containing abnormal cells significantly increased with age, and AL rats
had significantly more ETS abnormalities than CR rats at matched ages.
PCR amplification of mtDNA from kidney homogenates identified smaller
than wild-type mtDNA in the 36-month kidney but not in the 18-month.
We will use laser-capture microdissection of cells from normal and
abnormal tubules to determine whether deletion mutations are associated
with ETS abnormal renal tubular epithelial cells. Our data suggest
that both the structural changes and mitochondrial abnormalities that
develop in old rat kidneys are attenuated by adult-onset CR.
Key words:
rat, kidney, calorie restriction, mitochondria
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